吲哚布芬四氢异喹啉衍生物的设计、合成及生物活性研究
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摘要
依据药物化学中的拼合原理,本文设计了3个吲哚布芬四氢异喹啉衍生物,通过氯化反应、酰胺化反应、Bischler-Napieralski反应等步骤对设计化合物进行了合成,所合成目标化合物均经~1H-NMR、~(13)C-NMR、MS谱图佐证。采用Born比浊法测试了所合成目标化合物体外抗血小板聚集活性,其中化合物8b对AA和ADP诱导的血小板聚集显示了较好的活性,其IC50为1. 7 mmol·L~(-1)和6. 2 mmol·L~(-1),均优于阳性对照药阿司匹林。
Three indobufen tetrahydroisoquinoline derivatives based on combination principles were designed. They were synthesized by reaction chlorination,acylation reaction and Bischler-Napieralski reaction. The structures of three derivatives were identified by ~1H-NMR,~(13)C-NMR,MS. The targets compounds were tested for antiplatelet aggregation by Born turbidimetry method. The compound 8b showed a better activity against AA and ADP inducing platelet aggregation than aspirin,the IC50 value were 1. 7 mmol·L~(-1)and 6. 2mmol·L~(-1).
Three indobufen tetrahydroisoquinoline derivatives based on combination principles were designed. They were synthesized by reaction chlorination,acylation reaction and Bischler-Napieralski reaction. The structures of three derivatives were identified by ~1H-NMR,~(13)C-NMR,MS. The targets compounds were tested for antiplatelet aggregation by Born turbidimetry method. The compound 8b showed a better activity against AA and ADP inducing platelet aggregation than aspirin,the IC50 value were 1. 7 mmol·L~(-1)and 6. 2mmol·L~(-1).
引文
[1]陈伟伟,隋辉,马丽媛.中国心脑血管病流行现况及防治进展[J].心脑血管病防治,2016(2):79-83.
[2]黄伟军,胡敏华,李家明,等.基于抗血小板聚集的新型吡考他胺类似物的合成及其活性研究[J].化学试剂,2014(7):599-602.
[3]杨霞,刘维,陈恳,等.吲哚布芬片预防和治疗缺血性心脑血管病变有效性和安全性的Meta分析[J].中国临床药理学杂志,2017(4):359-362.
[4]Liu J,Xu D,Xia N,et al. Anticoagulant activities of Indobufen,an antiplatelet drug[J]. Molecules,2018(6):1451-1462.
[5]李丰,王杰,李家明,等.吲哚布芬酯类化合物的设计与合成[J].安徽医药,2015(2):233-235.
[6]Madhavi Gangapuram,Riccardo Jean,Elizabeth Mazzio,et al. Substituted tetrahydroisoquinolines as microtubule-destabilizing agents in triple negative human breast cancer cells[J]. Anticancer Research,2016(10):5043-5052.
[7]谢迪,张恩立,李家明,等.川芎嗪四氢异喹啉类化合物的设计、合成及其抗血小板聚集活性[J].药学学报,2015(3):326-331.
[8]Yang J,Hua W Y,Wang F X,et al. Design,synthesis,and inhibition of platelet aggregation for some 1-o-chlorophenyl-1,2,3,4-tetrahydroisoquinoline derivatives[J]. Bioorganic&Medicinal Chemistry,2004(24):6547-6557.
[9]朱盼虎,张艳春,李家明,等.四氢异喹啉类化合物的设计合成与体外抗肿瘤活性研究[J].中国新药杂志,2017(11):1301-1307.
[10]黄志强,王媞媞,刘秀杰. 4-甲氧基-1,3-苯二磺酸酯类化合物的合成及其体外抗血小板聚集活性[J].中国药物化学杂志,2017(4):274-278.
[2]黄伟军,胡敏华,李家明,等.基于抗血小板聚集的新型吡考他胺类似物的合成及其活性研究[J].化学试剂,2014(7):599-602.
[3]杨霞,刘维,陈恳,等.吲哚布芬片预防和治疗缺血性心脑血管病变有效性和安全性的Meta分析[J].中国临床药理学杂志,2017(4):359-362.
[4]Liu J,Xu D,Xia N,et al. Anticoagulant activities of Indobufen,an antiplatelet drug[J]. Molecules,2018(6):1451-1462.
[5]李丰,王杰,李家明,等.吲哚布芬酯类化合物的设计与合成[J].安徽医药,2015(2):233-235.
[6]Madhavi Gangapuram,Riccardo Jean,Elizabeth Mazzio,et al. Substituted tetrahydroisoquinolines as microtubule-destabilizing agents in triple negative human breast cancer cells[J]. Anticancer Research,2016(10):5043-5052.
[7]谢迪,张恩立,李家明,等.川芎嗪四氢异喹啉类化合物的设计、合成及其抗血小板聚集活性[J].药学学报,2015(3):326-331.
[8]Yang J,Hua W Y,Wang F X,et al. Design,synthesis,and inhibition of platelet aggregation for some 1-o-chlorophenyl-1,2,3,4-tetrahydroisoquinoline derivatives[J]. Bioorganic&Medicinal Chemistry,2004(24):6547-6557.
[9]朱盼虎,张艳春,李家明,等.四氢异喹啉类化合物的设计合成与体外抗肿瘤活性研究[J].中国新药杂志,2017(11):1301-1307.
[10]黄志强,王媞媞,刘秀杰. 4-甲氧基-1,3-苯二磺酸酯类化合物的合成及其体外抗血小板聚集活性[J].中国药物化学杂志,2017(4):274-278.